New data from an ongoing study indicates that the BluePrint functional molecular subtyping assay by Agendia, Irvine, Calif, more accurately identifies molecular subgroups and may be a better guide for neoadjuvant chemotherapy than standard, local immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays.


Pat Whitworth, MD, Nashville Breast Center

The report of interim study results from the Neoadjuvant Breast Registry Symphony Trial (NBRST) was selected for podium presentation by organizers of the 2015 Miami Breast Cancer Conference, which took place February 27 to March 1, in Miami Beach, Fla. The session, “Can we expand the pool of patients who may respond to Trastuzumab? Results of the NBRST trial using an 80-gene functional assay,” was presented by Pat Whitworth, MD, a Nashville surgical oncologist and principal investigator for the study.1

The aim of the prospective NBRST study is to compare functional molecular subtyping using Agendia’s BluePrint and MammaPrint assays to conventional local IHC and FISH subtyping for the prediction of chemosensitivity as defined by pathologic complete response (pCR).

“BluePrint gives us a more accurate picture of which patients may or may not respond to neoadjuvant chemotherapy by reclassifying up to 22% of tumors, and also helps suggest the best course for therapy,” says Whitworth. “One implication of the study findings is that we will eventually end up evaluating and treating many breast cancer patients differently than we do now, because we will rely on their functional molecular subtype rather than just IHC/FISH pathology results.”

Interim results for the first 426 patients in the NBRST study were published last year in the Annals of Surgical Oncology.2 Patients were classified into one of four molecular subgroups (basal, HER2, luminal A, luminal B), using Agendia’s BluePrint and Mammaprint assays, or using IHC/FISH subtyping. Analysis of the early study data found that the pathological complete response (pCR) rate to neoadjuvant chemotherapy (NCT) for HER2 patients classified by BluePrint and MammaPrint was 53%, whereas the pCR rate to NCT for HER2 patients classified by IHC/FISH assays was only 38% (p=0.047). In this instance, the authors thus judged classification by BluePrint and MammaPrint to be significantly superior to classification by IHC/FISH. Overall, wrote the authors, the findings suggest that “compared with IHC/FISH, BluePrint more accurately identifies patients likely to respond (or not respond) to NCT.”


Jan Egberts, MD, Agendia

Agendia’s BluePrint 80-gene molecular subtyping assay is the most widely available test providing the functional molecular subtype of a woman’s breast cancer. BluePrint is performed on formalin-fixed paraffin-embedded (FFPE) tissue and is part of Agendia’s suite of breast cancer assays that also includes the MammaPrint 70-gene risk of recurrence assay, which recently received FDA 510(k) clearance for use in FFPE tissue samples. MammaPrint was the first breast cancer risk of recurrence multigene assay to receive FDA 510(k) clearance. With the most recent clearance, Agendia now has six FDA clearances in its breast cancer portfolio.

Physicians and their patients typically rely on a number of factors when selecting the best course of therapy. “Agendia’s suite of breast cancer recurrence assays fundamentally changes that conversation at that critical point where treatment decisions are being made,” says Jan Egberts, MD, Agendia CEO. “While MammaPrint test results eliminate the ambiguity of the ‘intermediate result’ seen in up to 39% of other tests, molecular subtyping by BluePrint provides greater insight into the biology of the tumor that just isn’t available from most of the other breast cancer recurrence assays on the market.”

Agendia is a privately held molecular diagnostics company that develops and markets FFPE-based genomic diagnostic products. The company’s breast cancer suite includes MammaPrint, an FDA-cleared FFPE breast cancer recurrence assay; BluePrint, a molecular subtyping assay that provides deeper insight leading to more clinically actionable biology; and TargetPrint, an ER/PR/HER2 expression assay. MammaPrint has substantial insurance coverage, including Medicare, regional, and national insurers, encompassing an estimated 200 million lives in the United States.

These tests can help physicians assess a patient’s individual risk for metastasis—that is, which patients are more sensitive to chemo, hormonal, or combination therapy; which patients may not require these treatments; and which patients may be treated with other, less arduous and costly methods.

For more information, visit Agendia.


  1. Whitworth P. Can we expand the pool of patients who may respond to Trastuzumab? Results of the NBRST trial using an 80-gene functional assay. Miami Beach, Fla.: 2015 Miami Breast Cancer Conference, 27 February 2015.
  1. Whitworth P, Stork-Sloots L, de Snoo FA, et al. Chemosensitivity predicted by BluePrint 80-gene functional subtype and MammaPrint in the prospective Neoadjuvant Breast Registry Symphony Trial (NBRST). Ann Surg Oncol. 2014;21(10):3261–3267; doi: 10.1245/s10434-014-3908-y.